This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. (in collaboration with Dr. Elizabeth Seaquist, Medicine, supported by R01 NS035192, PI Seaquist): The overall goal of this project is to determine the effects of diabetes and the hypoglycemic consequences of intensive therapy on in vivo brain glucose metabolism in humans. In this grant cycle, we study glycogen metabolism in the human brain by 13C MR spectroscopy in conjunction with infusions of 13C-glucose. We first determined the glycogen content and turnover rate in healthy volunteers during eu- and slight hyperglycemia. We then investigated the role of brain glycogen during hypoglycemia. We hypothesized that the human brain utilizes glycogen during hypoglycemia and overshoots it to above normal levels ("supercompensates") following hypoglycemia, as was shown to occur in rodents. Understanding the role of glycogen in the human brain during and following hypoglycemia is important because glycogen supercompensation may be involved in hypoglycemia unawareness which is a major barrier to insulin treatment in patients with diabetes.